In order to induce the production of an objective antibody specific to an antigen in living bodies, a purified antigen has been conventionally administered alone or along with an immunological adjuvant (which means a substance enhancing the immunological reaction specific to an antigen by non-specific stimulation of immune system) to living bodies. Such method has frequently used for preventing various infectious diseases, and been considered as the most effective method because it is also effective even in the case of treating antibiotic-resistant diseases such as diseases caused by viruses or toxins produced from microorganisms. Particularly, in such case, the method thought to be the only effective treatment because it enables to defend the living bodies from such diseases by inducing the production of objective antibodies specific to viruses and toxins. At present, the method is practically applied to produce vaccines including inactivated vaccines (inactivated microbes without infecting activity, which are prepared by treating with an organic solvent or irradiating UV) and attenuated vaccines (attenuated pathogens with a weak pathogenicity against living bodies). The almost vaccines (except polio vaccines) have been parenterally administered by injection. Some inactivated vaccines, however, have problems of significant affection to living bodies and less convenience because they require successive injection for several times to obtain sufficient antibody titer to attain a satisfactory biophylaxis.
While, live vaccines such as the attenuated vaccines have problems that they have a low preservation-stability and a possibility to become harmful virulent mutants after administered to affect living bodies. Both of the inactivated vaccines and the live vaccines must be concerned to be unsafe because they may give an anaphylactic shock to living bodies. Further, human serum albumin or gelatin has been conventionally used as a stabilizer and often added to vaccine preparations containing instable virus particles or huge sized proteins as immunogens to improve the stability of the vaccine preparations. However, such substances must be also concerned to be unsafe because they possibly bring unknown infectious microorganisms or anaphylactic shock. Most of the vaccine preparations have been produced for injection use. However, vaccine preparations have been required to be more stable and applicable without injection in order to be commercialized widely all over the developing countries where many people are dying of infectious diseases.
To solve the above problems, new type vaccines, having higher safeness and efficacy than conventional inactivated vaccines or live vaccines, has been eagerly studied all over the world by using a polypeptide comprising a partial amino acid sequence of an inactivated vaccine or live vaccine. Such new type vaccines are developed as B type hepatitis viral vaccines such as a recombinant vaccine and component vaccine. Peptides used as new type vaccines are usually desired to be a short fragment. However, excessively short fragments are difficult to be designed to have a broad major histocompatibility antigen (hereinafter, abbreviated as “MHC”) class II restriction and satisfactory immunogenicity. While, in a view of enhancing immunogenicity of an objective antigen by permucosal administration, Lavelle, E. C. proposed in Immunology, Vol. 99, pp. 30-37, (2000) an immunizing method of an antigen with an immunological adjuvant such as cholera toxin (abbreviated as “CT”, hereinafter), heat-instable type of enterotoxin from E. coli, or attenuated proteins thereof prepared by replacing a part of the amino acid sequence of CT or enterotoxin. The method enables to obtain a sufficient induction of the objective antibodies. However it has not been practical because it undesirably brings the induction of antibodies specific to CT and heat-instable type of enterotoxin from E. coli as immunological adjuvants.
Dental caries and periodontal diseases are considered as the two major diseases caused by microorganisms in dental field. Since such diseases are universal and less critical, they should be prevented and treated under the highest safeness. As examples of the methods for preventing dental caries, Japanese Patent Publication Kokai No. 122,633/94 discloses a passive immunizing method using an antibody obtained from an animal immunized with a peptide fragment of a tooth surface adhesive protein from Streptococcus mutans, and Japanese Patent Publication Kokai No. 511,422/02 discloses an anti-dental caries vaccine composed of a T cell epitope and a B cell epitope of glucan binding protein from Streptococcus mutans. 
The present inventor had studied for the purpose of developing a short polypeptide which efficiently induces an antibody specific to cell surface protein antigen from Streptococcus mutans serotype C strain (It is abbreviated to “PAc”, hereinafter.), which relates to early phase adhesion to the tooth surface, for many individuals having different MHC class II haplotype by permucosal administration even in the absence of immunological adjuvant. In the detail field, for the purpose of enhancing the production of antibodies capable of preventing dental caries, the inventor proposed to design the short polypeptide in the manner of linearly linking a T cell epitope having multiple restrictions from several MHC class II haplotypes to N-terminus of the partial amino acid sequence of PAc at the positions of 365 to 377 (SEQ ID NO:1) as a B cell epitope with a dipeptide linker such as a lysine-lysine sequence (Nishizawa. T., Imai, S., and Hanada, N., Japanese Vaccine conference program abstract, p. 77, (2000), Oishi Y. et al., Oral Microbiology and Immunology, Vol. 16, pp. 40-44, (2001)). However, even the polypeptide disclosed in the above reference does not have enough immunogenicity to induce the production of the antibody. Therefore, the above problems of conventional peptide vaccines have not still been solved. Japanese Patent Publication Kokai No. 504,118/96 discloses a synthesized peptide vaccine enabling to prevent infection of Chlamydia trachomatis, which designed by linking a B cell epitope to the carboxyl terminal side of a T cell epitope. However, the vaccine did not satisfactorily induce the production of the antibody when permucosally administered.
Under the above circumstance, the object of the present invention is to provide a peptide vaccine, which satisfactorily induces the production of an antibody in living bodies and safely applicable to living bodies even when permucosally administered.